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Therapeutic Advances in Vaccines and... 2023Needle pain due to routine vaccination is an important factor contributing to low vaccine adherence and immunization coverage. Prophylactic oral analgesics can address...
Efficacy of oral mefenamic acid paracetamol as a prophylactic analgesic for needle pain in children receiving vaccination: a three-arm, parallel, triple-blind, placebo-controlled MAP VaC randomized controlled trial.
BACKGROUND
Needle pain due to routine vaccination is an important factor contributing to low vaccine adherence and immunization coverage. Prophylactic oral analgesics can address this important issue of needle pain related to vaccination. Paracetamol and mefenamic acid are commonly used nonsteroidal anti-inflammatory drugs for pain relief, but there is little published literature on whether the same can be used for needle pain related to vaccination.
OBJECTIVES
This study was planned to compare the efficacy of oral mefenamic acid and paracetamol over placebo as a prophylactic analgesic during vaccination and prophylactic antipyretic during the post-vaccination period.
DESIGNS
Three-arm, triple-blind, randomized controlled trial.
METHODS
This study was conducted at the outpatient department of a tertiary-level medical college in South India from January 2021 to June 2022. In this three-arm interventional trial, each arm had either a single dose of placebo or mefenamic acid (4 mg/kg/dose) or paracetamol (10 mg/kg/dose). These medicines were administered orally 30 min before vaccination to reduce needle pain.
MAIN OUTCOME AND MEASURES
Outcome was measured with the change of FLACC (Face, Leg, Activity, Cry, Consolability) scoring at the time of vaccination, subsequently at 15 and 30 min of vaccination in all three groups. Appearance of fever, grade of fever, and need for antipyretics 24 h after vaccination were also noted.
RESULTS
There was a significant difference in FLACC scores at the time of administration ( = 0.010) and at 15 min ( = 0.014) with mefenamic acid compared to placebo. Although the paracetamol group showed a difference when compared to the placebo, it was not significant at the time of administration ( = 0.401), at 15 min ( = 0.451), or 30 min ( = 0.892) post-vaccination. The appearance of fever, grade of fever, and use of antipyretic up to 24 h post-vaccination had no significant difference among any of the three groups.
CONCLUSION
Mefenamic acid was more potent than placebo for pre-vaccination pain prophylaxis in children. There was no difference in the appearance of fever and its grade among the three groups. The promising results from this trial warrant further large-scale studies to recommend a single oral dose of mefenamic acid to tackle needle pain related to vaccination in children to improve vaccine adherence and coverage.
TRIAL REGISTRATION
CTRI (Clinical trials registry-India) (CTRI/2021/01/030239). [Date of Commencement: 13 Jan 2021, Date of last recruitment: 30 June 2022 (now closed for new participants)].
PubMed: 38077267
DOI: 10.1177/25151355231216122 -
ACS Omega Dec 2023The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a...
Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure-Activity Relationship, Kinetics Mechanism, and In Silico Studies.
The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a dynamic field of study and advancement within medicinal chemistry. This research demonstrates the conjugation of diclofenac and mefenamic acid with sulfa drugs and their screening for urease inhibition. These conjugates' structural confirmation was performed using elemental analysis and spectroscopic methods, including IR, H NMR, and C NMR. Diclofenac conjugated with sulfanilamide (4), sulfacetamide (10), and mefenamic acid conjugated with sulfanilamide (12), and sulfamethoxazole (17) was found potent and demonstrated urease inhibition competitively, with IC (μM) values 3.59 ± 0.07, 5.49 ± 0.34, 7.92 ± 0.27, and 8.35 ± 0.26, respectively. Diclofenac conjugated with sulfathiazole (6), sulfamerazine (8), and sulfaguanidine (11), while mefenamic acid conjugated with sulfisoxazole (13), sulfathiazole (14), and sulfadiazine (15) exhibited a mixed mode of urease inhibition. The IC (μM) values were 16.19 ± 0.21, 9.50 ± 0.28, 4.35 ± 0.23, 15.86 ± 0.25, 14.80 ± 0.27, and 7.92 ± 0.27, respectively. Furthermore, molecular docking studies were employed to predict the binding pose of competitive inhibitors at the urease active site. These conjugates generated stable complexes with the urease protein observed through molecular dynamics (MD) simulations, where no conformational changes occurred throughout the simulations. These results highlight the potential for approved therapeutic molecule conjugates to give rise to new categories of pharmacological agents for urease inhibition. The structural similarity of sulfonamides with urea allows them to compete with urea for binding to the active site of the urease enzyme. Sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) can interact hydrophobically with the active site of the urease enzyme, which may disturb its structure and catalytic activity. Therefore, these conjugates may be helpful in the development of novel pharmacological agents for the treatment of a variety of illnesses in which the urease enzyme is involved.
PubMed: 38075833
DOI: 10.1021/acsomega.3c07275 -
Journal of Mid-life Health 2023Abnormal uterine bleeding (AUB) is a common problem in reproductive age group and perimenopausal age group being responsible for many outpatient visits. Traditional...
To Study the Efficacy and Safety of Diosmin with Tranexamic Acid and Mefenamic Acid Versus only Tranexamic Acid and Mefenamic Acid in Medical Management of Abnormal Uterine Bleeding: A Randomized Controlled Trial.
BACKGROUND
Abnormal uterine bleeding (AUB) is a common problem in reproductive age group and perimenopausal age group being responsible for many outpatient visits. Traditional management of AUB consists of giving mefenamic acid, tranexamic acid, or their combination with progestogens or hormonal intrauterine deviced levonorgestrel intrauterine system (LNG-IUS) for severe or nonresponsive cases. The objective of the current study was to study the efficacy and safety of adding diosmin along with tranexamic acid and mefenamic acid in reducing menstrual blood loss in AUB patients.
MATERIALS AND METHODS
It was a prospective double-blind randomized controlled trial in which 900 mg of diosmin was given once daily along with 500 mg tranexamic acid and 250 mg mefenamic acid during menstruation (Group I-92 patients), or only tranexamic acid and mefenamic acid during menstruation (Group II-92 patients).
RESULTS
Mean age, parity, body mass index, and socioeconomic status were similar in the two groups. It was 35.68 years versus 36.78 years, 2.2 versus 2.3, 23.68 kg/m versus 24.62 kg/m respectively. Mean days of bleeding before this treatment were 6.8 versus 6.6 ( = 0.33) and were 3.5 versus 5.2 ( = 0.02) after treatment. There was a significant reduction in both groups as compared to before treatment ( = 0.021 in Group I, 0.027 in Group II) but the reduction was greater in Group I ( = 0.02). The amount of blood loss was 385 ml versus 390 ml ( = 0.7) before treatment which was significantly reduced in both groups to 68 ml versus 112 ml ( = 0.02 in Group I, 0.03 in Group II) with more decrease in Group I than in Group II ( = 0.01). Mean hemoglobin at beginning of the study was 8.4 versus 8.5 g/dl in Group I and Group II ( = 0.02) and significantly increased in both groups posttreatment to 10.9 and 9.8 g/dl in Group I and Group II ( = 0.012 in Group I, 0.011 in Group II) with increase being more in Group I than Group II ( = 0.03). Pictorial blood assessment chart score was 398 versus 406 ( = 0.35) before treatment and decreased significantly to 86.5 and 110.5 ( = 0.001 in Group I, 0.001 in Group II) with more decrease being in Group I than II ( = 0.01). There was significant decrease in dysmenorrhea with both treatments with no difference in the two groups. Various adverse effects such as nausea, vomiting, abdominal pain, diarrhea, constipation, and headache were equal in the two groups.
CONCLUSION
Both the group's diosmin with tranexamic acid and mefenamic acid (Group I) and tranexamic acid and mefenamic acid (Group II) were efficacious in reducing menstrual blood loss, number of menstrual days and dysmenorrhea with effect being more by addition of diosmin. Adverse effects were equal in both the two groups.
PubMed: 38029032
DOI: 10.4103/jmh.jmh_253_22 -
Journal of Cancer Research and Clinical... Dec 2023This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. I was utilized as a radiolabeling isotope...
BACKGROUND
This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. I was utilized as a radiolabeling isotope to study the radio-kinetics of MEF niosomes.
METHODS
niosomal formulations were prepared by the ether injection method and assessed for entrapment efficiency (EE%), zeta potential (ZP), polydispersity index (PDI) and particle size (PS). MEF was labeled with I by direct electrophilic substitution reaction through optimization of radiolabeling-related parameters. In the radio-kinetic study, the optimal I-MEF niosomal formula was administered intravenously (I.V.) to solid tumor-bearing mice and compared to I.V. I-MEF solution as a control.
RESULTS
the average PS and ZP values of the optimal formulation were 247.23 ± 2.32 nm and - 28.3 ± 1.21, respectively. The highest I-MEF labeling yield was 98.7 ± 0.8%. The biodistribution study revealed that the highest tumor uptake of I-MEF niosomal formula and I-MEF solution at 60 min post-injection were 2.73 and 1.94% ID/g, respectively.
CONCLUSION
MEF-loaded niosomes could be a hopeful candidate in cancer treatment due to their potent tumor uptake. Such high targeting was attributed to passive targeting of the nanosized niosomes and confirmed by radiokinetic evaluation.
Topics: Mice; Animals; Liposomes; Mefenamic Acid; Tissue Distribution; Neoplasms
PubMed: 37982828
DOI: 10.1007/s00432-023-05482-8 -
Health Technology Assessment... Oct 2023Heavy menstrual bleeding is a common problem that can significantly affect women's lives until menopause. There is a lack of evidence on longer-term outcomes after... (Observational Study)
Observational Study
BACKGROUND
Heavy menstrual bleeding is a common problem that can significantly affect women's lives until menopause. There is a lack of evidence on longer-term outcomes after seeking health care and treatment for heavy menstrual bleeding.
OBJECTIVES
To assess the continuation rates of medical treatments and the rates of ablative and surgical interventions among women who had participated in the ECLIPSE trial (ISRCTN86566246) 10 years after initial management for heavy menstrual bleeding in primary care. To explore experiences of heavy menstrual bleeding and influences on treatment for women.
DESIGN
This was a prospective observational cohort study, with a parallel qualitative study.
SETTING
Primary care.
PARTICIPANTS
A total of 206 women with heavy menstrual bleeding who had participated in the ECLIPSE trial consented to providing outcome data via a questionnaire approximately 10 years after original randomisation. Their mean age at follow-up was 54 years (standard deviation 5 years). A purposeful sample of 36 women also participated in semistructured qualitative interviews.
INTERVENTIONS
The ECLIPSE trial randomised participants to either the levonorgestrel-releasing intrauterine system (52 mg) or the usual medical treatment (oral tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone, chosen as clinically appropriate by general practitioners and women). Women could subsequently swap or cease their allocated treatment.
MAIN OUTCOME MEASURES
The main outcome measures were rates of ablative and surgical treatments; the rate of continuation of medical treatments; and quality of life using the Short Form questionnaire-36 items and EuroQol-5 Dimensions; women's experiences of heavy menstrual bleeding; and the influences on their decisions around treatment.
RESULTS
Over the 10-year follow-up period, 60 out of 206 (29%) women had received a surgical intervention [hysterectomy, = 34 (17%); endometrial ablation, = 26 (13%)]. Between 5 and 10 years post trial intervention, 89 women (43%) had ceased all medical treatments and 88 (43%) were using the levonorgestrel-releasing intrauterine system alone or in combination with other oral treatments. More women in the usual medical treatment group had also used the levonorgestrel-releasing intrauterine system than women in the levonorgestrel-releasing intrauterine system group. Fifty-six women (28%) used the levonorgestrel-releasing intrauterine system at 10 years. There was no statistically significant difference in generic quality-of-life scores between the two original trial groups, although small improvements in the majority of domains were seen in both groups across time. Women reported wide-ranging impacts on their quality of life and normalisation of their heavy menstrual bleeding experience as a result of the taboo around menstruation. Women's treatment decisions and experiences were influenced by the perceived quality of health-care interactions with clinicians and their climacteric status.
LIMITATIONS
Fewer than half of the original 571 participants participated; however, the cohort was clinically and demographically representative of the original trial population.
CONCLUSIONS
Medical treatments for women with heavy menstrual bleeding can be initiated in primary care, with low rates of surgical intervention and improvement in quality of life observed 10 years later. Clinicians should be aware of the considerable challenges that women with heavy menstrual bleeding experience at presentation and subsequently over time, and the importance and value to women of patient-centred communication in this context.
FUTURE WORK
Any further evaluation of treatments for heavy menstrual bleeding should include long-term evaluation of outcomes and adherence.
TRIAL REGISTRATION
The original ECLIPSE trial was registered as ISRCTN86566246.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 27, No. 17. See the NIHR Journals Library website for further project information.
Topics: Female; Humans; Middle Aged; Follow-Up Studies; Intrauterine Devices, Medicated; Levonorgestrel; Menorrhagia; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 37924269
DOI: 10.3310/JHSW0174 -
European Journal of Pharmaceutics and... Dec 2023Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in...
Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in vitro is limited and multiple simulated intestinal fluid recipes have been developed but with no consensus which is optimal. This study has utilised nine bioequivalent simulated fed intestinal media recipes that cover over 90% of the compositional variability of sampled fed human intestinal fluid. The solubility of 24 drugs (Acidic; furosemide, ibuprofen, indomethacin, mefenamic acid, naproxen, phenytoin, piroxicam, valsartan, zafirlukast: Basic; aprepitant, atazanavir, bromocriptine, carvedilol, dipyridamole, posaconazole, tadalafil: Neutral; acyclovir, carbamazepine, felodipine, fenofibrate, griseofulvin, itraconazole, paracetamol, probucol) has been assessed to determine if structured solubility behaviour is present. The measured solubility behaviour can be split into four categories and is consistent with drug physicochemical properties and previous solubility studies. For acidic drugs (category 1) solubility is controlled by media pH and the lowest and highest pH media identify the lowest and highest solubility in 90% of cases. For weakly acidic, basic and neutral drugs (category 2) solubility is controlled by media pH and total amphiphile concentration (TAC), a consistent solubility pattern is evident with variation related to individual drug media component interactions. The lowest and highest pH × TAC media identify the lowest and highest solubility in 70% and 90% of cases respectively. Four drugs, which are non-ionised in the media systems (category 3), have been identified with a very narrow solubility range, indicating minimal impact of the simulated media on solubility. Three drugs exhibit solubility behaviour that is not consistent with the remainder (category 4). The results indicate that the use of two bioequivalent fed intestinal media from the original nine will identify in vitro the maximum and minimum solubility values for the majority of drugs and due to the media derivation this is probably applicable in vivo. When combined with a previous fasted study, this introduces interesting possibilities to measure a solubility range in vitro that can provide Quality by Design based decisions to rationalise drug and formulation development. Overall this indicates that the multi-dimensional media system is worthy of further investigation as in vitro tool to assess fed intestinal solubility.
Topics: Humans; Solubility; Hydrogen-Ion Concentration; Intestines; Pharmaceutical Preparations; Indomethacin; Intestinal Absorption
PubMed: 37890541
DOI: 10.1016/j.ejpb.2023.10.017 -
Iranian Endodontic Journal 2023This study aimed to compare the efficacy of ibuprofen, Novafen, mefenamic acid (MA), and celecoxib for pain relief in patients with symptomatic irreversible pulpitis... (Review)
Review
Comparative Efficacy of Analgesics for Pain Relief in Patients with Symptomatic Irreversible Pulpitis Prior to Emergency Endodontic Treatment: A Randomized Controlled Trial.
INTRODUCTION
This study aimed to compare the efficacy of ibuprofen, Novafen, mefenamic acid (MA), and celecoxib for pain relief in patients with symptomatic irreversible pulpitis prior to emergency endodontic treatment.
MATERIALS AND METHODS
This clinical trial was conducted on 120 patients with moderate to severe pain due to symptomatic irreversible pulpitis seeking emergency endodontic treatment. The patients were randomly divided into 4 groups to receive Novafen, MA, Celecoxib, and ibuprofen. The pain score of patients was measured before and 1 hour after analgesic intake using a visual analog scale (VAS). The success of analgesic treatment was analyzed by the binary logistic regression model.
RESULTS
A total of 117 patients including 76 females and 41 males with a mean age of 30.29 years completed the study and were statistically analyzed. Ibuprofen had the highest analgesic efficacy followed by Novafen, and caused a significantly greater reduction in pain score compared with MA and celecoxib [OR (Ibuprofen vs MA)=1.28, OR (Ibuprofen vs Celecoxib)=3.74, OR (Novafen vs MA)=2.94, OR (Novafen vs Celecoxib)=2.94, <0.05]. Ibuprofen and Novafen had no significant difference in analgesic efficacy (>0.05). Baseline pain score was a predictive factor for the success of analgesics (<0.05). The success of analgesic treatment decreased by 0.68 times with each unit increase in pain score (<0.05). Gender and age of patients had no significant effect on success of analgesics (>0.05).
CONCLUSION
Both ibuprofen and Novafen can serve as the analgesics of choice for pain relief in patients with symptomatic irreversible pulpitis with moderate to severe pain when emergency endodontic treatment cannot be immediately performed.
PubMed: 37829826
DOI: 10.22037/iej.v18i4.35469 -
CPT: Pharmacometrics & Systems... Jan 2024Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the...
Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate-glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug-drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically-based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling. A PBPK model of vericiguat was developed based on in vitro and clinical data, verified against data from the mefenamic acid DDI study, and applied to assess the UGT1A1 DDI liability by running an in silico DDI study with the UGT1A1 inhibitor atazanavir. A minor effect with an area under the plasma concentration-time curve (AUC) ratio of 1.12 and a peak plasma concentration ratio of 1.04 was predicted, which indicates that there is no clinically relevant DDI interaction anticipated. Additionally, the effect of potential genetic polymorphisms of UGT1A1 and UGT1A9 was evaluated, which showed that an average modest increase of up to 1.7-fold in AUC may be expected in the case of concomitantly reduced UGT1A1 and UGT1A9 activity for subpopulations expressing non-wild-type variants for both isoforms. This study is a first cornerstone to qualify the PK-Sim platform for use of UGT-mediated DDI predictions, including PBPK models of perpetrators, such as mefenamic acid and atazanavir, and sensitive UGT substrates, such as dapagliflozin and raltegravir.
Topics: Humans; Atazanavir Sulfate; Mefenamic Acid; Glucuronosyltransferase; Drug Interactions; Heterocyclic Compounds, 2-Ring; Pyrimidines
PubMed: 37794724
DOI: 10.1002/psp4.13059 -
Toxics Aug 2023Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent...
Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent antioxidant properties and a neuroprotective effect against oxidative stress. However, its impact on the liver is unclear. This study aimed to elucidate the antioxidative effects of MFA and their underlying mechanisms. We observed that MFA treatment upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Treatment with various anthranilic acid derivative-class NSAIDs, including MFA, increased the expression of sequestosome 1 (SQSTM1) in HepG2 cells. MFA disrupted the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, activating the Nrf2 signaling pathway. SQTM1 knockdown experiments revealed that the effect of MFA on the Nrf2 pathway was masked in the absence of SQSTM1. To assess the cytoprotective effect of MFA, we employed tert-Butyl hydroperoxide (tBHP) as a ROS inducer. Notably, MFA exhibited a protective effect against tBHP-induced cytotoxicity in HepG2 cells. This cytoprotective effect was abolished when SQSTM1 was knocked down, suggesting the involvement of SQSTM1 in mediating the protective effect of MFA against tBHP-induced toxicity. In conclusion, this study demonstrated that MFA exhibits cytoprotective effects by upregulating SQSTM1 and activating the Nrf2 pathway. These findings improve our understanding of the pharmacological actions of MFA and highlight its potential as a therapeutic agent for oxidative stress-related conditions.
PubMed: 37755745
DOI: 10.3390/toxics11090735 -
Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E